Análise de Custo-Efetividade da Terapia com Evolocumabe em Pacientes com Alto Risco de Eventos Cardiovasculares no Contexto do SUS - Brasil / Cost-Effectiveness Analysis of Evolocumab Therapy in Patients at High Risk of Cardiovascular Events in the Context of the Brazilian Unified Health System

Resumo Fundamento: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. Objetivo: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. Métodos: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. Resultados: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. Conclusões: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.

Abstract Background: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice / Própolis e natação na prevenção da aterogênese e hipertrofia ventricular esquerda de camundongos hipercolesterolêmicos

Aims The present study verified the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice. Methods and Results The experiments were performed in LDLr–/– mice, fed with high fat diet for 75 days, and were divided into four experimental groups (n=10): HL, sedentary, subjected to aquatic stress (5 min per day, 5 times per week); NAT submitted to a swimming protocol (1 hour per day, 5 times per week) from the 16th day of the experiment; PRO, sedentary, submitted to aquatic stress and which received oral propolis extract (70 uL/animal/day) from the 16th day of the experiment; HL+NAT+PRO, submitted to swimming and which received propolis as described above. After 75 days, blood was collected for analysis of serum lipids. The ratio between the ventricular weight (mg) and the animal weight (g) was calculated. Histological sections of the heart and aorta were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process; stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The HL animals showed severe dyslipidemia, atherogenesis and left ventricular hypertrophy, associated with a decrease in serum HDLc levels and subsequent development of cardiovascular inflammatory process, characterized by increased expression of CD40L in the left ventricle and aorta. Swimming and propolis alone and/or associated prevented the LVH, atherogenesis and arterial and ventricular inflammation, decreasing the CD40L expression and increasing the HDLc plasmatic levels. Conclusion Propolis alone or associated with a regular physical activity is beneficial in cardiovascular protection through anti-inflammatory action. .

Objetivos O presente estudo verificou o efeito do própolis associação ou não com a natação na dislipidemia, na hipertrofia ventricular esquerda e aterogênese de camundongos hipercolesterolêmicos. Métodos e Resultados Os experimentos foram realizados em camundongos LDLr–/–, alimentados com dieta hiperlipídica por 75 dias, e divididos em quatro grupos experimentais (n = 10): HL, sedentários, foram submetidos ao estresse aquático (5 min por dia, cinco vezes por semana); NAT foram submetidos a um protocolo de natação (1 hora por dia, cinco vezes por semana) a partir do 16° dia do experimento; PRO, sedentários, submetidos a estresse aquático e que receberam extrato de própolis oral (70 uL / animal / dia) a partir do 16° dia do experimento; HL + NAC + PRO, submetidos a natação e que recebeu a própolis, como descrito acima. Após 75 dias, foi coletado sangue para análise do perfil lipídico. Calculou-se a relação entre o peso ventricular (mg) e o peso do animal (g). Os cortes histológicos do coração e aorta foram processados imunohistoquímicamente com anticorpos anti-CD40L para avaliar o processo inflamatório, corados com hematoxilina / eosina e picrossírius red, para avaliar as alterações morfológicas e morfométricas. Os camundongos HL apresentaram dislipidemia grave, aterogênese e hipertrofia do ventrículo esquerdo, associada a uma diminuição dos níveis plasmáticos de HDLc e o desenvolvimento subsequente do processo inflamatório cardiovasculares, caracterizada pelo aumento da expressão do CD40L no ventrículo esquerdo e na aorta. Natação e a própolis isolado e / ou associados preveniram a HVE, a aterogênese e a inflamação tanto na artéria quanto no ventrículo, diminuindo a expressão de CD40L, aumentando os níveis plasmáticos de HDLc. Conclusão A Própolis isolada ou associada a uma atividade física regular é benéfica na proteção cardiovascular através da ação anti-inflamatória. .

Cardiac and renal effects induced by different exercise workloads in renovascular hypertensive rats

We examined the effect of exercise training (Ex) without (Ex 0 percent) or with a 3 percent workload (Ex 3 percent) on different cardiac and renal parameters in renovascular hypertensive (2K1C) male Fisher rats weighing 150-200 g. Ex was performed for 5 weeks, 1 h/day, 5 days/week. Ex 0 percent or Ex 3 percent induced similar attenuation of baseline mean arterial pressure (MAP, 119 ± 5 mmHg in 2K1C Ex 0 percent, N = 6, and 118 ± 5 mmHg in 2K1C Ex 3 percent, N = 11, vs 99 ± 4 mmHg in sham sedentary (Sham Sed) controls, N = 10) and heart rate (HR, bpm) (383 ± 13 in 2K1C Ex 0 percent, N = 6, and 390 ± 14 in 2K1C Ex 3 percent, N = 11 vs 371 ± 11 in Sham Sed, N = 10,). Ex 0 percent, but not Ex 3 percent, improved baroreflex bradycardia (0.26 ± 0.06 ms/mmHg, N = 6, vs 0.09 ± 0.03 ms/mmHg in 2K1C Sed, N = 11). Morphometric evaluation suggested concentric left ventricle hypertrophy in sedentary 2K1C rats. Ex 0 percent prevented concentric cardiac hypertrophy, increased cardiomyocyte diameter and decreased cardiac vasculature thickness in 2K1C rats. In contrast, in 2K1C, Ex 3 percent reduced the concentric remodeling and prevented the increase in cardiac vasculature wall thickness, decreased the cardiomyocyte diameter and increased collagen deposition. Renal morphometric analysis showed that Ex 3 percent induced an increase in vasculature wall thickness and collagen deposition in the left kidney of 2K1C rats. These data suggest that Ex 0 percent has more beneficial effects than Ex 3 percent in renovascular hypertensive rats.

Efectividad del uso combinado de un inhibidor de Rho Kinasa y de un antagonista del receptor de angiotensina II en la prevención de hipertrofia ventricular en ratas hipertensas / Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats

La actividad de Rho kinasa (ROCK) cardíaca en la hipertensión arterial (HTA) y el efecto del tratamiento antihipertensivo conjunto han sido poco estudiados. Hemos planteado que la adición de un inhibidor de ROCK al tratamiento antihipertensivo convencional podría tener efectos preventivos adicionales al uso aislado del antihipertensivo. Objetivo: Determinar la actividad de ROCK ventricular y parámetros de remodelamiento cardíaco en ratas hipertensas con y sin tratamiento antihipertensivo, adicionando un inhibidor directo de ROCK. Métodos. Se usaron ratas Sprague Dawley de 150 grs. ( n = 12 - 13/grupo) unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc) durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Otros 3 grupos recibieron DOCA y además el antagonista del receptor de angiotensina n, candesartán (10 mg/kg/día) o el inhibidor de la vía ROCK fasudil (50 mg/Kg/dia), o la combinación de ambos (5 y 25 mg/Kg/dia, respectivamente), vía gavage desde la tercera semana post cirugía, durante 3 semanas. Al finalizar los tratamientos se determinó la masa corporal (MC), presión arterial sistólica (PAS) y la masa cardíaca relativa (MCR). Además se midió en el ventrículo izquierdo la fosforilación de la fosfatasa de la miosina (MYPT-1) como índice de activación de ROCK, la infiltración de macrófagos/ monocitos (células ED1 positivas), la expresión proteica de colágeno I (por Western blot) y la expresión génica de la subunidad gp91 de NADPH oxidasa y eNOS por RTPCR. Resultados: Con respecto de las ratas sham, en las ratas hipertensas se observó hipertrofia cardiaca de 63 por ciento (p < 0,05), junto a aumento significativo (p < 0,05) de MYPT-1 fosforilado/total (300 por ciento), de colágeno miocárdico I (en 14 veces), de células ED1 en 270 por ciento y de la expresión génica de la subunidad gp91 de NADPH...

Background: The effect of cardiac Rho-kinase (ROCK) on hypertension (HT) and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additional beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks). Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day) or the combination of both agents (5 and 25 mg/kg/day, respectively) and ROCK inhibitor fasudil (50 mg/kg/day) for 3 weeks starting 3 weeks after surgery. Body mass (BM), systolic blood pressure (SBP) and relative cardiac mass (RCM) were measured. In addition, myosin phosphatase (MYPT-1) phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells), collagen I protein contení (by Western Blot) and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63 percent (p < 0.05), a 300 percent increase in cardiac MYPT-1 phosphorylation (p< 0.05), 14 times increase in myocardial collagen type 1,270 percent increase in ED1 cells, a 75 percent increased gene expression of NADPH oxydase GP91 subunit and a 37 percent reduction (p< 0.05) in the gene expression of cardiac eNOS. In hypertensive DOCA rats treated during 3 week with candesartan, fasudil or the combination of both, we observed a significant reduction in cardiac hypertrophy and normalization of SBP, MYPT-1 phosphorylation, ...

Spironolactone effects on myocardium changes induced by thyroid hormone in rats / Efeitos da espironolactona sobre as alterações miocárdicas induzidas pelo hormônio tireoideano em ratos

FUNDAMENTO: Estudar o papel do sistema renina-angiotensina-aldosterona na hipertrofia miocárdica induzida pelo hormônio tireoideano, utilizando-se a espironolactona. OBJETIVO: Analisar as alterações morfológicas no miocárdio induzidas pelo hormônio tireoideano e os efeitos da espironolactona nesse processo. MÉTODOS: Foram estudados 40 ratos Wistar, divididos em quatro grupos, que receberam: veículo utilizado para a diluição do hormônio tireoideano (C); levotiroxina sódica (50 µg/rato/dia) (H); espironolactona (0,3 mg/kg/dia) (E) e hormônio tireoideano + espironolactona (HE), nas mesmas doses citadas, durante 28 dias consecutivos. Todos os animais foram submetidos a pesagem, coleta de sangue para dosagens hormonais e realização de ECG no início e no final do experimento. Ao final do período de estudo, os animais foram sacrificados para determinação do peso do ventrículo esquerdo (VE) e obtenção de cortes de VE para análise morfológica. RESULTADOS: Houve aumento dos níveis de T3 no plasma, perda de peso corporal e aumento da freqüência cardíaca nos animais que receberam o hormônio. O peso do VE foi maior nos grupos H e HE. A análise histométrica mostrou maiores diâmetros dos miócitos no grupo H, com os valores decrescentes nos grupos HE, E e C, sendo as diferenças estatisticamente significantes entre todos os grupos. A espironolactona associada ao hormônio tireoideano (HT) diminuiu em 14,6 por cento a hipertrofia transversal dos miócitos. CONCLUSÃO: Em ratos tratados com hormônio tireoideano ocorre hipertrofia cardíaca com aumento do peso do VE e do diâmetro do miócito. A associação de espironolactona ao hormônio tireoideano previne parcialmente essa hipertrofia por mecanismos ainda desconhecidos.

BACKGROUND: To study the possible role of aldosterone on thyroid hormone-induced myocardium hypertrophy, using spironolactone. OBJECTIVE: To evaluate morphological changes in the myocardium induced by thyroid hormone and the possible effects of spironolactone use on these alterations. METHODS: Forty Wistar rats were studied. The animals were allocated to four groups and were given: the vehicle used for dilution of the thyroid hormone (C); sodium levothyroxin at 50 µg/rat/day (H); spironolactone, 0.3 mg/kg/day (S); or thyroid hormone plus spironolactone (HS), at the same doses mentioned above, for 28 consecutive days. All the animals were weighed, had blood drawn for hormonal measurements and underwent ECG at the start and the end of the experiment. At the end of experiment all animals were euthanized, the weight of the left ventricle (LV) was determined and LV slices were obtained for morphological analysis. RESULTS: There was an increase in T3 levels, decrease of body weight and higher heart rate in the animals from group H. The LV weight was significantly higher in the H e HS groups. The histometric analyses that measured the diameter of the myocytes showed higher values in group H and a progressive decrease in groups HS, S and C, with a significant difference among all the groups. The addition of spironolactone decreased the transversal myocyte hypertrophy by 14.6 percent. CONCLUSION: Rats treated with thyroid hormone present cardiac hypertrophy with increased LV weight and greater myocyte diameter. Spironolactone, when associated with thyroid hormone, can partially prevent this hypertrophy through mechanisms that are yet to be determined.

Estudo ecocardiográfico evolutivo das alterações anátomo-funcionais do coração em obesos submetidos à cirurgia bariátrica / Evolutive echocardiographic study of the structural and functional heart alterations in obese individuals after bariatric surgery

OBJETIVO: Avaliar com a Dopplerecocardiografia a reversibilidade das alterações estruturais e funcionais do coração em obesos submetidos à cirurgia bariátrica. MÉTODOS: Foram estudados 23 obesos (19 mulheres: 82,6 por cento) com idade média de 37,9 anos. Tinham obesidade classe III ou classe II com co-morbidades. Realizaram avaliação clínica e ecocardiográfica no pré-operatório, 6 meses e 3 anos após a cirurgia. RESULTADOS: Antes da operação o peso era de 128,7 ± 25,8 kg e a pressão arterial (PA) 142,2 ± 16,2/92,2 ± 10,4 mmHg. No pós-operatório houve redução do peso aos 6 meses (97,6 ± 18,3 Kg) e aos 3 anos (83,6 ± 13,5 Kg), e da PA aos 6 meses (128,5 ± 16,1/80,7 ± 9,9 mmHg) com resultado mantido em 3 anos. Ao ecocardiograma, antes da cirurgia havia hipertrofia da parede posterior do ventrículo esquerdo (VE) e septo interventricular, com dimensão diastólica do VE normal e padrão geométrico predominante de remodelamento concêntrico (74 por cento). Após 6 meses, diminuíram as espessuras do septo e da parede posterior, e aumentou a dimensão diastólica do VE. Em 3 anos o padrão geométrico predominante era o normal (69 por cento), com redução da massa de VE e do índice de massa do VE/altura² . Observou-se também melhora da função diastólica de VE, com aumento da relação E/A em 6 meses, mantendo-se em 3 anos e diminuição do tempo de relaxamento isovolumétrico do VE em 6 meses e em 3 anos. Houve melhora do índice de Desempenho Miocárdico em 6 meses, mantendo-se em 3 anos, em 13 pacientes estudados retrospectivamente. Notou-se aumento do tempo de ejeção em 6 meses, mantendo-se em 3 anos, e discreto aumento da fração de ejeção em 3 anos, sugerindo melhora da função sistólica de VE. CONCLUSÃO: A redução de peso obtida através da cirurgia para obesidade promove modificações estruturais e funcionais benéficas ao coração.

OBJECTIVE: To evaluate with Doppler echocardiography the reversibility of structural and hemodynamic changes in obeses after bariatric surgery. METHODS: Twenty-three patients (19 women = 82.6 percent) were studied. Mean age was 37.9 years. All subjects had Class III or Class II obesity with comorbidity and were submitted to bariatric surgery. Clinical and echocardiographic evaluation were performed preoperatively, in 6 months and 3 years after surgery. RESULTS: Preoperatively, the mean weight and blood pressure (BP) were respectively 128.7± 25.8 kg and 142.2 ± 16.2 / 92.2 ± 10.4 mmHg. Postoperatively, they showed important body weight reduction in 6 months (97.6 ± 18.3 kg) and 3 years (83.6 ± 13.5 kg), and BP reduction in 6 months (128.5 ± 16.1/80.7 ± 9.9 mmHg) that remain stable in 3rd year. On echocardiogram, preoperatively, there was hypertrophy of the septum and posterior wall associated with normal diastolic dimension; the predominant LV geometric pattern was concentric remodeling (74 percent). At six months, thinning of the ventricular septum and LV posterior wall, and increase in LV diastolic dimension were demonstrated. At 3rd year, the predominant LV pattern was normal (69 percent), with reduction of LV mass and LV mass/height² index. We noticed improved diastolic function, with an increased E/A ratio and a decreased LV isovolumic relaxation time. The Myocardial Performance Index was obtained retrospectively in 13 patients and improved in 6 months. There was an increase of the ejection time in 6 months and an elevation of the ejection fraction in 3rd year, suggesting improvement of the LV systolic function. CONCLUSION: The weight loss obtained with bariatric surgery promotes both structural and functional myocardial changes that improve cardiac performance.

Efficacy of Irbesartan on Left Ventricular Mass and Arterial Stiffness in Hypertensive Patients

BACKGROUND: Increased aortic stiffness measured by pulse wave velocity (PWV) and left ventricular hypertrophy (LVH) are independent risk factors of cardiovascular events in hypertensive patients. We have conducted a prospective study to examine the effects of the angiotensin II receptor antagonist (irbesartan) on PWV and LVH in hypertensive patients. METHODS: A total of 52 untreated hypertensive patients (age:53.3+/-8.0 yrs) were enrolled; they had no evidence of associated cardiovascular complications. Blood pressure, heart rate, aortic PWV and left ventricular mass index (LVMI) by 2-D echocardiography were measured at baseline and after irbesartan treatment (150 mg or 300 mg/day) at 12 weeks and 24 weeks. RESULTS: Blood pressure was significantly decreased after 12 weeks and 24 weeks of treatment compared to baseline (SBP: 134.6+/-13.3 mmHg, 134.0+/-11.0 mmHg vs 163.7+/-13.8 mmHg p<0.001, DBP: 86.0+/-10 mmHg, 83.07 mmHg vs 102.4+/-9.6 mmHg p<0.001, respectively) without significant change in heart rate. LVMI decreased at 12 weeks and at 24 weeks after treatment compared to baseline (from 145.5+/-35.1 g/m2 at baseline to 137.5+/-35.4 g/m2 at 12 weeks, p=0.017 and 135.3+/-35.4 g/m2 at 24 weeks, p=0.008). Aortic PWV was decreased after irbesartan treatment at 12 weeks (from 9.6+/-2.8 m/sec to 8.7+/-3.1 m/sec at 12 weeks, p=0.064) and at 24 weeks (from 9.6+/-2.9 m/sec to 7.7+/-2.1 m/sec at 24 weeks, p=0.007). CONCLUSIONS: Long-term treatment with irbesartan may reduce arterial stiffness and regression of LVH in hypertensive patients. The pleiotropic effects of irbesartan, further decreasing PWV without change of BP between 12 and 24 weeks of treatment, may have favorable vascular effects on arterial stiffness and LVH.

O bloqueio do sistema renina-angiotensina atenua a remodelação cardíaca de ratos submetidos a estenose aórtica / Blockade of renin-angiotensin system attenuates cardiac remodeling in rats undergoing aortic stenosis

OBJETIVO: Avaliar o papel do bloqueador dos receptores AT1 e do inibidor da enzima conversora da angiotensina na remodelação cardíaca induzida por estenose aórtica em ratos. MÉTODOS: Ratos Wistar foram divididos em 4 grupos: controle (C, n=13), estenose aórtica (EAo, n=11), EAo com lisinopril, 20 mg/kg/dia (LIS, n=11) e EAo com losartan, 40 mg/kg/dia (LOS, n=9). Os tratamentos foram iniciados 3 dias antes da cirurgia. Após 6 semanas, os animais foram submetidos ao estudo ecocardiográfico, quantificação da concentração de hidroxiprolina e da área seccional (CSA) miocitária do ventrículo esquerdo (VE). RESULTADOS: A EAo induziu aumento da espessura da parede do VE. Os animais LIS e LOS não apresentaram diferença em relação aos animais controles. Os ratos EAo e LIS apresentaram maiores diâmetros do átrio esquerdo que os ratos controles, enquanto nos animais LOS não houve diferença. Os animais com EAo apresentaram maiores valores da porcentagem de encurtamento que os controle. Esse fato não foi modificado com LIS ou LOS. A CSA dos animais do grupo EAo foi maior que a dos controle. Entretanto, o tratamento com LOS e com LIS atenuou o aumento da área induzida pela EAo. A EAo resultou em aumento na concentração de HOP, enquanto o grupo LOS não apresentou diferença em relação ao grupo controle. CONCLUSÃO: O bloqueio do sistema renina-angiotensina, com bloqueador AT1 e com IECA, pode atenuar o desenvolvimento de hipertrofia cardíaca, porém só o bloqueio dos receptores AT1 atenua a fibrose intersticial do VE.

Proteção miocárdica pelo ramipril na hipertrofia ventricular esquerda: estudo experimental / Protective effect of ramipril on the left ventricle hypertrophy: experimental study

Introdução: A hipertrofia patológica do ventrículo esquerdo é um poderoso e independente fator de risco para complicações cardiovasculares, estando relacionada com aumento de duas a cinco vezes o risco de infarto do miocárdio, seis a dezessete vezes o risco de insuficiência cardíaca e três a dez vezes o risco de acidente vascular cerebral. Objetivo: avaliar em ratos se o ramipril na dose de 1mg/kg/dia apresenta efeito protetor sobre a hipertrofia do ventrículo esquerdo (HVE), induzida pelo isoproterenol (ISO), administrado por via subcutânea (0,3mg/kg/dia). Método: formados quatro grupos de ratos machos e adultos, com 14 exemplares em cada um, sendo o primeiro o grupo controle (CON), segundo o tratado com ramipril (RAM); o grupo seguinte com isoproterenol (ISO) e o último tratado com ambas as drogas (RAM + ISO). Aferidos: o peso úmido do ventrículo esquerdo (PUVE), peso seco do ventrículo esquerdo (PSVE), relação PSVE pelo peso do animal (PSVE/P) e o índice de massa do ventrículo esquerdo (IMVE). Retiradas amostras do ventrículo esquerdo dos animais para estudo morfológico pela microscopia de luz, e em três animais de cada grupo um fragmento foi processado para estudo ultra-estrutural. Resultados: em relação ao PSVE obtiveram-se os seguintes resultados: Grupo CON: 0,14486; Grupo RAM: 0,13771; Grupo ISO: 0,20400; Grupo RAM + ISO: 0,16000; com diferença significante entre o grupo ISO e os demais (p<0, 05). A análise do PSVE/P demonstrou o mesmo comportamento. Na avaliação microscópica de luz e eletrônica de transmissão, observou-se proteção da HVE no Grupo RAM+ISO, em relação ao grupo ISO Conclusões: as análises morfológica e ultra-estrutural demonstraram que isoproterenol induz hipertrofia dos cardiomiócitos e aumento do tecido conjuntivo, com acentuados depósitos de fibras colágenas No grupo RAM + ISO observou-se ação protetora em relação à hipertrofia muscular e a depósitos de colágeno O uso isolado de ramipril não provocou alterações no que diz respeito ao...

The changes in cardiac dimensions and function in patients with end stage renal disease undergoing hemodialysis

BACKGROUND: It is absolutely necessary to evaluate cardiac function on starting and during hemodialysis in patients with end stage renal disease. In this study, we tried to determinate the changes of cardiac function associated with hemodialysis. METHODS: Twenty patients with end stage renal disease, who had been in a hemodialysis program from February, 1997 to August, 1999 in Pusan National University Hospital, were enrolled. They were examined with echocardiography and gated blood pool scintigraphy on starting hemodialysis and after follow-up. The data were analyzed by paired t-test. RESULTS: The patients were 46.2 +/- 16.8 years old and male to female ratio was 8 : 12. The underlying diseases were diabetes mellitus (n=10), hypertension1), glomerulonephritis2) and others1). The duration of symptoms associated with end stage renal disease and underlying diseases was 3.4 2.6 years and the duration of hemodialysis was 13.8 7.0 months. The LVEDID, LVESID and RVC decreased significantly (-6.10, -7.80 and -20.00%, respectively, p 0.05). In ten cases associated with diabetes, LVEDID decreased (-7.90%, p < 0.05). In twelve cases associated with cardiac diseases, LVEDID and LVESID decreased (-8.60 and -10.50%, respectively, p < 0.05). In four cases associated with diabetes without cardiac diseases, LAD decreased (-5.10%, p 0.05) and in four cases associated with cardiac diseases without diabetes there were no significant changes in cardiac dimensions and EF. In seven cases associated with diabetes and cardiac diseases, LVEDID decreased (-10.50%, p < 0.05). The EF on gated blood pool scintigraphy decreased (-0.9%, p < 0.05) as a whole while it increased (5.90%, p < 0.05) in the cases associated with diabetes and cardiac diseases. CONCLUSION: During the early hemodialysis stage of end stage renal disease, we found a change of concentric left ventricular hypertrophy and relatively preserved left ventricular function. Furthermore, we can expect that adequate hemodialysis - with dry weight as low as possible - may prevent progression to eccentric left ventricular hypertrophy and dilated cardiomyopathy.

Reduçäo da hipertrofia ventricular esquerda em pacientes com hipertensäo arterial com uso de inalapril, losartan ou a associaçäo enalapril + losartan / Reduction in left ventricualr hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enapril and losartan

OBJECTIVE : To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. METHODS : Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arte-rial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril 35 mg/day, n=15), losartan (175 mg/day, n=1 effective in reducing blood pressure and left ventricular mass index (LVMI, g/m2): 141ñ3.9 to 123ñ3.6 in the enalapril group (p<0.05), from 147ñ3.8 to 133ñ2.8 in the losartan group (p<0.05), and from 146ñ3.0 to5) and enalapril+losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. RESULTS : The three therapeutic regimens were equally 116ñ4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5ñ5.0 per cent) than in enalapril (12.4ñ3.2 per cent) and the losartan (9.1ñ2.1 per cent) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who reinhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin. (Au)ceived enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15patients treated with losartan. CONCLUSION : The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

Prevençäo da hipertrofia ventricular esquerda em ratos induzida pelo isoproterenol: comparaçäo entre Ramipril e Losartan / Prevention of left ventricular hypertrophy in rats induced by isoproterenol: the relationship between Ramipril and Losartan

Obetivo: Avaliar comparativamente a capacidade do losartan (bloqueador do receptor AT1 da angiotensina II) e o ramipril (inibidor da enzima de conversäo da angiotensina) em prevenir a hipertrofia ventricular esquerda induzida por isoproterenol em ratos. Métodos: Foram estudados 64 ratos divididos em 4 grupos por um período de 15 dias, após foram sacrificados e comparados através dos pesos dos ventrículos e estudo anatomo-patologico. Resultados: Os animais tratados com losartan apresentaram pesos dos ventrículos esquerdos menores com significância estatística, assim como menor tamanho das fibras miocárdicas e menos colágeno quando comparados aos tratados com ramipril. Conclusäo: O losartan foi superior ao ramipril na prevençäo da hipertrofia ventricular esquerda induzida por isoproterenol em ratos.

Left ventricular muscle mass regression after aortic valve replacement

Implanting a valve that will reduce left ventricular mass is critical in aortic stenosis. Regression of left ventricular hypertrophy in 46 aortic valve replacement (AVR) patients receiving a St. Jude Medical (SJM) valve was assessed by serial electrocardiographic and echocardiographic studies during the preoperative, immediate, and late postoperative periods. The patients were divided into three groups according to valve size; 19 mm group (n=9), 21 mm group (n=20), and 23+mm group (n=17). There was no surgical mortality. The NYHA functional class improved from an average of 2.2+/-0.8 preoperatively to 1.3+/-0.5 post-operatively. Left ventricular muscle mass index (LVMI) regression failed to reach statistical significance in the 19 mm group, whereas in the other two groups a steady decrease in the LVMI occurred with follow up. ECG findings were less remarkable showing insignificant differences in voltage among the three groups (p=0.000). In conclusion, the current data suggest that the 19 mm SJM valve may not result in satisfactory left ventricular muscle mass regression despite adequate function, even in small patients. Therefore, additional procedures to accommodate a larger valve may be warranted in the aortic annulus smaller than 21 mm.